The objective of this study will be to define new factors of adrenocortical origin in human hypertensive disease. Efforts by several investigators to identify a new steroid with mineralocorticoid properties in low renin hypertension has not yet been successful. We feel that the best evidence to date for the existence of an unknown mineralocorticoid in man comes from patients studied in this laboratory. We have developed new data which demonstrate that certain patients have increased hypertension with ACTH stimulation. Amelioration of blood pressure with aminoglutethimide and dexamethasone suggests that the ACTH-stimulable hypertension is due to an adrenal steroid. Urinary aldosterone increased with ACTH administration. Yet administration of the known mineralocorticoids (aldosterone, DOC or 18-OH-DOC) did not raise blood pressure when the adrenal was suppressed with dexamethasone and blood pressure was normal. The failure to elevate blood in spite of marked sodium retention and weight gain suggests that a yet unidentified hormone was causative of the hypertension in the untreated state and after ACTH. This hypothesis was strengthened by the demonstration of hypertension and hypokalemia in a patient deficient in all known corticoids. ACTH increased the blood pressure with no increase in aldosterone excretion. Normalization of blood pressure and hypokalemic alkalosis with spironolactone suggests that there is secretion of an unknown hypertensive factor in this disorder of remarkably high potency. We plan to identify and characterize this factor and seek its presence in other forms of hypertension.